TY - JOUR
T1 - A common breakpoint on 11q23 in carriers of the constitutional t(11;22) translocation
AU - Edelmann, L.
AU - Spiteri, E.
AU - McCain, N.
AU - Goldberg, R.
AU - Pandita, R. K.
AU - Duong, S.
AU - Fox, J.
AU - Blumenthal, D.
AU - Lalani, S. R.
AU - Shaffer, L. G.
AU - Morrow, B. E.
N1 - Funding Information:
We thank Drs. Alan Shanske, Birgit Funke, and Jose Ferreira for their helpful discussions. We would like to thank Ms. Catherine Kashork for help in performing the FISH mapping (Baylor College of Medicine). This work was supported by grant PO-1 HD34980-3 from the National Institutes of Health (NIH) and by grant FY98-0414 from the March of Dimes. L.E. was supported by grant T32 CA09060 from the NIH.
PY - 1999
Y1 - 1999
N2 - Structural chromosomal rearrangements occur commonly in the general population. Individuals that carry a balanced translocation are at risk of having unbalanced offspring; therefore, the frequency of translocations in couples with recurrent spontaneous abortions is higher than that in the general population. The constitutional t(11;22) translocation is the most common recurrent non-Robertsonian translocation in humans and may serve as a model to determine the mechanism that causes recurrent meiotic translocations. We previously localized the t(11;22) translocation breakpoint to a region on 22q11 within a low-copy repeat, termed 'LCR22'. To define the breakpoint on 11q23 and to ascertain whether this region shares homology with LCR22 sequences, we performed haplotype analysis on patients with der(22) syndrome. We found that the breakpoint on 11q23 occurred between two genetic markers, D11S1340 and APOC3-tetra, both being present within a single bacterial-artificial-chromosome clone. To determine whether the breakpoint occurred within the same region among a larger set of carriers, we performed FISH mapping studies. The breakpoints were all within the same clone, suggesting that this region may harbor sequences that are prone to breakage. We narrowed the breakpoint interval, in both derivative chromosomes from two unrelated carriers, to a 190-bp, AT-rich repeat, which indicates that this repeat may mediate recombination events on chromosome 11. Interestingly, the LCR22s harbor AT-rich repeats, suggesting that this sequence motif may mediate recombination events in nonhomologous chromosomes during meiosis.
AB - Structural chromosomal rearrangements occur commonly in the general population. Individuals that carry a balanced translocation are at risk of having unbalanced offspring; therefore, the frequency of translocations in couples with recurrent spontaneous abortions is higher than that in the general population. The constitutional t(11;22) translocation is the most common recurrent non-Robertsonian translocation in humans and may serve as a model to determine the mechanism that causes recurrent meiotic translocations. We previously localized the t(11;22) translocation breakpoint to a region on 22q11 within a low-copy repeat, termed 'LCR22'. To define the breakpoint on 11q23 and to ascertain whether this region shares homology with LCR22 sequences, we performed haplotype analysis on patients with der(22) syndrome. We found that the breakpoint on 11q23 occurred between two genetic markers, D11S1340 and APOC3-tetra, both being present within a single bacterial-artificial-chromosome clone. To determine whether the breakpoint occurred within the same region among a larger set of carriers, we performed FISH mapping studies. The breakpoints were all within the same clone, suggesting that this region may harbor sequences that are prone to breakage. We narrowed the breakpoint interval, in both derivative chromosomes from two unrelated carriers, to a 190-bp, AT-rich repeat, which indicates that this repeat may mediate recombination events on chromosome 11. Interestingly, the LCR22s harbor AT-rich repeats, suggesting that this sequence motif may mediate recombination events in nonhomologous chromosomes during meiosis.
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U2 - 10.1086/302689
DO - 10.1086/302689
M3 - Article
C2 - 10577914
AN - SCOPUS:0033358603
SN - 0002-9297
VL - 65
SP - 1608
EP - 1616
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -